Prior to the present invention, there have existed mechanical structures and vessels for the simultaneous testing of separately supported pharmaceutical tablets tested for rate or required times of disintegration or for time of dissolution in liquid media such as water, as supporting vessels are moved therethrough. Required times are recorded as observed by a worker who intermittently checks the progress--noting that some disintegrations require extended times, sometimes hours, rather than a mere few minutes. Not only does such procedure tie-down valuable workers needed for and normally assigned to other duties concurrently, but the mere fact that such observations are intermittent at best, the recorded times and observations are most likely highly unreliable and inexact, as to true times of actual disintegration.
For testing disintegration rate, the prior art test is provided to determine federal compliance with the limits on disintegration stated in the individual monographs except and where the label states that the tablets or capsules are intended for use as troches, or are to be chewed, or are designed to liberate the drug content gradually over a period of time or to release the drug over two or more separate periods with a distinct time interval between such release periods. The type of units under test is determined from the labeling and from observation, and the appropriate prior art procedure is applied to six or more dosage units.
For disintegration purposes for this type test(s), disintegration does not imply complete solution of the unit or even of its active constituent. Complete disintegration is defined as that stat in which any residue of the unit, except fragments of insoluble coating or capsule shell, remain on the screen of the test tablet-support apparatus in a soft mass having no palpably firm core.
A typical prior art apparatus for testing disintegration time(s) consists of a basket-rack assembly, a 1000 ml. low-form beaker for the immersion fluid, a thermostatic arrangement for heating the fluid between 35 and 39 degrees, i.e. about 37.5 degrees, Centigrade and a device for raising and lowering the basket in the immersion fluid at a constant frequency rate between 29 and 32 cycles per minute through a distance of not less than 5.3 cm. and not more than 5.7 cm.. The volume of the fluid in the vessel is such that at the highest point of the upward stroke the wire mesh (that supports the tablet(s) remains at least 2.5 cm below the surface of the fluid and descends to not less than 2.5 cm. from the bottom of the vessel on the downward stroke. The time required during the upward stroke is equal to the time required for the downward stroke, and the change in stroke direction is a smooth transition rather than an abrupt reversal motion. The basket-rack(s) support-assembly(ies) move substantially vertically along its(their) vertical axis(axes). There is no appreciable horizontal motion or movement of the axis from the vertical.
For the disintegration assembly, the basket rack assembly of the prior art typically consists of six open-ended glass tubes, each 7.75 cm. (plus or minus 0.24 cm.) in length and having an inside diameter of approximately 21.5 mm and a wall approximately 2 mm. thickness. The tubes are held in a vertical position by two plastic plates, each about 9 cm in diameter and 6 mm. in thickness, with six holes, each about 24 mm. in diameter, equidistant from the center of the plate and equally spaced from one another. Attached to the under surface of the lower plate is a 10-mesh (typically) No. 23 (0.025 inch) W. and M. gauge woven stainless steel wire cloth having typically a plain square weave. The prior art parts of the apparatus are assembled and are rigidly held by bolts passing through two plastic plates with suitable mechanical mechanism being provided to suspend the basket-rack assembly from the raising and lowering device.
For disintegration procedure with the above-noted mechanical mechanism, there are separate procedures followed for each of different types of tablets, such as for uncoated tablets, and plain coated tablets, and for enteric-coated tablets, and for buccal tablets, and for sublingual tablets, and the like. It is not a purpose nor function of the present invention described hereinafter to distinguish between nor alter such procedures.
For disintegration, a typical prior art disintegration tester is the Vanderkamp Tablet Disintegration Tester of VAN-KEL Industries, Inc., having a machine for alternately raising and lowering the basket(s), and including one power base with a single basket hanger, a basket-rack assembly, a set of six fluted plastic discs, a basket suspension rod, and disintegration beakers. A complete system includes a disintegration tester, a basket hanger, one or more racket assemblies, fluted plastic discs, basket suspension rods, and disintegration beakers. A six-basket system would include 6 basket capacity tester, six unit basket hanger, six basket rack assemblies, six sets of six fluted plastic discs, six basket suspension rods, and six disintegration beakers. These details are given for purposes of providing common knowlege and understanding of the state of the prior art. In this same context, there are available prior art water baths of clear acrylic or stainless steel typically ranging from 18 to 42 inches long, and typically twelve inches wide and eight inches deep. There are also available precision baths of typically square width-length dimensions. It is common for such various baths or liquid-vessels to include mechanisms and electrical wiring or circuitry as to provide temperature at temperatures that may be manually set or reset and/or maintained, and mechanisms for keeping the water stirred or circulated to assure constant temperature(s) throughout the liquid within the bath-vessel(s).
With regard to dissolution testing, a typical prior art tester is the Vanderkamp [registered trademark] 600 tester of VAN KEL Industries, Inc. in which several different groups of tablets are separately contained in separate support structures within a common liquid media of a common transparent waterbath(vessel), with a separate paddle provided and inserted from above, for each separately supported(contained) tablets--each one or more separately supported(contained) tablets being supported(contained) within typically an open-top transparent vessel having a rounded bottom. The above-noted typical prior art dissolution tester for an all six-spindle tester, includes one Vanderkamp (trademark) 600 including complete drive unit with four post assembly and flask covers, and six rotating basket assemblies [of USP Method (T-1045029)] or stainless steel teflon coated paddles [of USP Method II (T-1045-7037), and six 1000 ml. round bottom glass dissolution vessel (K-1010) or plastic dissolution vessels (K-1012), and one transparent waterbath of typically 3/8 inch acrylic, and one set of stainless steel locating gauges. A typical external bath circular model is available as an acrylic waterbath with circulator and tygon tubing. There is also alternately available such bath that is a "mounted" circular model having an acrylic waterbath with a circulator and a mounting frame. In these models, the circulating paddles and/or supports of the separate vessels, may individually or as a group be intermittently raised or lowered into or from the liquid media contained in the bath vessel. These dissolution baths likewise have associated therewith temperature sensors and mechanism for heating or maintaining temperature of the bath's liquid at temperature(s) that may be manually set.
With the prior art hardware and procedures above-noted, there have existed problems relating to both time requirements of workers to maintain constant observations monitoring of progressive disintegration(s) and/or dissolution(s) of set(s) of tablets, and questionable and/or unreliable results as reported that result from unreliable intermittent observation(s) made by observers making the occasional intermittent observation from time to time over sometimes a running period of many hours.
It is also a fact that casual personal observations are not always exact nor precise nor reliable in actual practice, and yet heretofore there has not existed any corrective hardware making possible more exact and reliable data. The task heretofore has been further complicated because of the fact of moving supports(containers) and/or baskets and/or paddles, associated with the tablets, by which exact observation is hampered.